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Melatonin and Multiple Sclerosis: From Plausible Neuropharmacological Mechanisms of Action to Experimental and Clinical Evidence

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Abstract

Multiple sclerosis (MS) is a devastating chronic autoimmune demyelinating disease of the central nervous system (CNS), thought to affect more than 2.5 million people worldwide. Regulation of the sleep-wake cycle might influence disease activity and the frequency of relapses in patients. As melatonin (or sleep hormone) involves the regulation of circadian rhythms, much attention has been paid to the management of MS symptoms with melatonin. This review describes the pharmacological mechanisms underlying the neuroprotective effects of melatonin and recent clinical evidence from MS patients. Apparent risks and benefits of melatonin therapies are also discussed. Various in vivo and clinical data presented in this up-to-date review suggest that melatonin may possibly possess a protective role against the behavioral deficits and neuropathological characteristics of MS. Multiple mechanisms of the neuroprotective effects of melatonin such as mitochondrial protection and antioxidant, anti-inflammatory, and anti-apoptotic properties, as well as its anti-demyelinating function are also discussed. A large body of evidence shows that melatonin potently regulates the immune system, demyelination, free radical generation, and inflammatory responses in neural tissue, which are mediated by multiple signal transduction cascades. In the present article, we focus on different pathways that are targeted by melatonin to prevent the development and progression of MS.

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Authors and Affiliations

  1. Student’s Research Committee, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Mahshid Yeganeh Salehpour

  2. Department of Pharmacy, University “G. d’ Annunzio” of Chieti-Pescara, Via Dei Vestini 31, 66100, Chieti, Italy

    Adriano Mollica

  3. Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran

    Saeideh Momtaz

  4. Pharmaceutical Sciences Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran

    Saeideh Momtaz

  5. Department of Biology, Faculty of Sciences, University of Zabol, Zabol, Iran

    Nima Sanadgol

  6. Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Mohammad Hosein Farzaei

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  1. Mahshid Yeganeh Salehpour
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Correspondence to Mohammad Hosein Farzaei.

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Yeganeh Salehpour, M., Mollica, A., Momtaz, S. et al. Melatonin and Multiple Sclerosis: From Plausible Neuropharmacological Mechanisms of Action to Experimental and Clinical Evidence. Clin Drug Investig 39, 607–624 (2019). https://doi.org/10.1007/s40261-019-00793-6

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